Our overall objective is to define the changes that occur in the types and quantities of enzymes in cells in the hemopoietic system during differentiation and as a result of genetic mutation or neoplastic transformation. We have extended our investigations to include studies of the thymocyte and lymphocyte in addition to erythrocytes and granulocytes. A major part of our research effort at the present time is devoted to a special type of deoxynucleotide polymerizing enzyme in thymocytes called terminal deoxynucleotide transferase (TdT). This enzyme may serve as a biochemical marker of the conversion of undifferentiated lymphocytes to T-cells. TdT may play a role in the programming of the variable region sequences in immunoglobulins. It also appears to be a marker enzyme in acute lymphoblastic leukemia and in certain types of acute nonlymphoblastic leukemias. We are interested in the use of this enzyme in diagnosis and prognosis of acute leukemia as well as its basic function in differentiation of hematopoietic cells. Other research at the present time is devoted to a description of changes in DNA polymerase, terminal transferase, adenosine deaminase and thymidine incorporation into thymocytes and lymphocytes from rats that have received immunosuppressive therapy. Some of these enzyme activities are also being measured in the lymphocytes of patients who have lymphoproliferative diseases.